tbuckley/cabot-search huggingface dataset:
Defining global strategies to improve outcomes in sickle cell disease: a Lancet Haematology Commission
Authors: Frédéric B Piel, David C Rees, Michael R DeBaun, Obiageli Nnodu, Brigitte Ranque, Alexis A Thompson, Russell E Ware, Miguel R Abboud, Allistair Abraham, Emmanuela E Ambrose, Biree Andemariam, Roshan Colah, Raffaella Colombatti, Nicola Conran, Fernando F Costa, Robert M Cronin, Mariane de Montalembert, Jacques Elion, Erica Esrick, Anthea L Greenway, Ibrahim M Idris, David-Zacharie Issom, Dipty Jain, Lori C Jordan, Zane S Kaplan, Allison A King, Michele Lloyd-Puryear, Samuel A Oppong, Akshay Sharma, Lillian Sung, Leon Tshilolo, Diana J Wilkie, Kwaku Ohene-Frempong
Journal: The Lancet Haematology (2023)
Heterochromatin-Dependent Replication Stress: A Lesson from IDH1/2 Mutants
Authors: Lee Zou
Journal: Cancer Research (2023)

Oncogenic point mutants of isocitrate dehydrogenases 1 and 2 (IDH2) generate 2-hydroxyglutarate, which inhibits lysine demethylases and increases heterochromatin. Tumor cells expressing IDH mutants are sensitive to PARP inhibitors (PARPi), offering an opportunity to eliminate IDH-driven tumor cells in therapy. Expression of an oncogenic IDH1 mutant in cells leads to aberrant heterochromatin formation at DNA breaks and impairs DNA repair through homologous recombination (HR), providing a possible explanation for the PARPi sensitivity of IDH mutant cells. However, a recent study published in Molecular Cell shows that IDH mutant tumors do not display the genomic alterations associated with HR defects. Instead, IDH mutants induce heterochromatin-dependent DNA replication stress. Furthermore, PARP is activated by the replication stress induced by IDH mutants and required for suppressing the ensuing DNA damage, providing an alternative model to explain the susceptibility of IDH mutant cells to PARPis. This study presents a new example of oncogene-induced and heterochromatin-dependent replication stress, and a role of PARP in the response to the stress, extending the molecular basis for PARP-targeted therapy.
Impact of Asian Race on Prognosis in De Novo Metastatic Prostate Cancer
Authors: Xudong Ni, Luu Michael, Weiwei Ma, Tingwei Zhang, Yu Wei, Stephen J. Freedland, Dingwei Ye, Timothy J. Daskivich, Yao Zhu
Journal: Journal of the National Comprehensive Cancer Network (2023)

Background: Little is known about the impact of Asian race on the long-term survival outcomes of males with de novo metastatic prostate cancer (PCa). Understanding racial disparities in survival is critical for accurate prognostic risk stratification and for informing the design of multiregional clinical trials. Methods: This multiple-cohort study included individual patient-level data for males with de novo metastatic PCa from the following 3 cohorts: LATITUDE clinical trial data (n=1,199), the SEER program (n=15,476), and the National Cancer Database (NCDB; n=10,366). Primary outcomes were overall survival (OS) in LATITUDE and NCDB and OS and cancer-specific survival in SEER. Results: Across all 3 cohorts, Asian patients diagnosed with de novo metastatic PCa had better survival than white patients. In LATITUDE, median OS was significantly longer in Asian versus white patients in the androgen deprivation therapy (ADT) + abiraterone + prednisone group (not reached vs 43.8 months; hazard ratio [HR], 0.45; 95% CI, 0.28–0.73; P =.001) as well as in the ADT + placebo group (57.6 vs 32.7 months; HR, 0.51; 95% CI, 0.33–0.78; P =.002). In SEER, among all patients diagnosed with de novo metastatic PCa, median OS was significantly longer in Asian versus white males (49 vs 39 months; HR, 0.76; 95% CI, 0.68–0.84; P &lt;.001). Among those who received chemotherapy, Asian patients again had longer OS (52 vs 42 months; HR, 0.71; 95% CI, 0.52–0.96; P =.025). Using data on cancer-specific survival in SEER resulted in similar conclusions. In NCDB, Asian patients also had longer OS than white patients in aggregate and in subgroups of males treated with ADT or chemotherapy (aggregate: 38 vs 26 months; HR, 0.72; 95% CI, 0.62–0.83; P &lt;.001; ADT subgroup: 41 vs 26 months; HR, 0.71; 95% CI, 0.60–0.84; P &lt;.001; chemotherapy subgroup: 34 vs 25 months; HR, 0.67; 95% CI, 0.57–0.78; P &lt;.001). Conclusions: Asian males have better OS and cancer-specific survival than white males with metastatic PCa across different treatment regimens. This should be considered when assessing prognosis and in designing multinational clinical trials.
Multiple Origins and Genomic Basis of Complex Traits in Sighthounds
Authors: Wu-Lue Li, Yan-Hu Liu, Jin-Xiu Li, Meng-Ting Ding, Adeniyi C Adeola, Jainagul Isakova, Almaz A Aldashev, Min-Sheng Peng, Xuezhen Huang, Guoli Xie, Xi Chen, Wei-Kang Yang, Wei-Wei Zhou, Zeinab Amiri Ghanatsaman, Sunday C Olaogun, Oscar J Sanke, Philip M Dawuda, Marjo K Hytönen, Hannes Lohi, Ali Esmailizadeh, Andrey D Poyarkov, Peter Savolainen, Guo-Dong Wang, Ya-Ping Zhang
Journal: Molecular Biology and Evolution (2023)

Sighthounds, a distinctive group of hounds comprising numerous breeds, have their origins rooted in ancient artificial selection of dogs. In this study, we performed genome sequencing for 123 sighthounds, including one breed from Africa, six breeds from Europe, two breeds from Russia, and four breeds and 12 village dogs from the Middle East. We gathered public genome data of five sighthounds and 98 other dogs as well as 31 gray wolves to pinpoint the origin and genes influencing the morphology of the sighthound genome. Population genomic analysis suggested that sighthounds originated from native dogs independently and were comprehensively admixed among breeds, supporting the multiple origins hypothesis of sighthounds. An additional 67 published ancient wolf genomes were added for gene flow detection. Results showed dramatic admixture of ancient wolves in African sighthounds, even more than with modern wolves. Whole-genome scan analysis identified 17 positively selected genes (PSGs) in the African population, 27 PSGs in the European population, and 54 PSGs in the Middle Eastern population. None of the PSGs overlapped in the three populations. Pooled PSGs of the three populations were significantly enriched in "regulation of release of sequestered calcium ion into cytosol" (gene ontology: 0051279), which is related to blood circulation and heart contraction. In addition, ESR1, JAK2, ADRB1, PRKCE, and CAMK2D were under positive selection in all three selected groups. This suggests that different PSGs in the same pathway contributed to the similar phenotype of sighthounds. We identified an ESR1 mutation (chr1: g.42,177,149 T > C) in the transcription factor (TF) binding site of Stat5a and a JAK2 mutation (chr1: g.93,277,007 T > A) in the TF binding site of Sox5. Functional experiments confirmed that the ESR1 and JAK2 mutation reduced their expression. Our results provide new insights into the domestication history and genomic basis of sighthounds.
Highlights of the NCCN Oncology Research Program
Authors: Anurag Singh, Sai Yendamuri, Elizabeth Bouchard
Journal: Journal of the National Comprehensive Cancer Network (2023)

Currently, patients with peripheral, early-stage non-small cell lung cancer (NSCLC) can be treated with surgery or stereotactic body radiation therapy (SBRT).Patients with inoperable NSCLC receive SBRT.However, there are many patients who are deemed operable but for whom surgery poses increased risk and therefore SBRT is a reasonable option.For these patients, it is unclear if surgery or SBRT provides better outcomes.Recent and ongoing clinical trials have attempted to randomize patients to surgery or radiation.Patients have been hesitant to allow randomization given the invasive nature of surgery and the noninvasive nature of SBRT; consequently, study recruitment has been difficult.Because evidence from randomized trials is unlikely to be available soon, this study focuses on factors other than oncologic outcomes but that are nevertheless important to patients.
Erratum
Authors: Gregory Riely, Wui-Jin Carlson, Katy Winckworth-Prejsnar
Journal: Journal of the National Comprehensive Cancer Network (2023)

the world, with more than 13 million downloads per year; nearly half of registered users of the NCCN Guidelines report that they live outside the United States.NCCN Harmonized Guidelines are based on the original versions of the NCCN Guidelines but also include color-coded modifications of the algorithms to represent both the optimal care that low-and mid-resource countries aspire to provide and pragmatic approaches that provide effective treatment options for resourceconstrained settings.NCCN Harmonized Guidelines have already been published in collaboration with local experts in Sub-Saharan Africa and the Caribbean."We look forward to building off the highly regarded NCCN Guidelines, taking into account our local circumstances, physiologic and risk differences, accessibility, regulations, and technology, to better serve people with cancer across Vietnam," said Professor Le Van Quang, Director and Chairperson of K Hospital."By making the highest standards in evidence-based care more accessible, we can help all of our patients to live better lives.
A qualitative exploration of patient experiences in pyoderma gangrenosum
Authors: Samantha Herbert, Reneé Haughton, William  Liakos, Jenny Wang, Antonio Ji-Xu, Stephanie T Le, Emanual Maverakis
Journal: British Journal of Dermatology (2023)

Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis that is associated with a decreased quality-of-life (QoL). There are no PG-specific patient-reported outcome measures. In this exploratory study, we use patient interviews to define QoL domains in PG that will inform future outcomes measures.
Determining PARP Inhibition as a Treatment Strategy in Melanoma Based on Homologous Recombination Deficiency–Related Loss of Heterozygosity
Authors: Alice Zhou, Omar Butt, Michael Ansstas, Elizabeth Mauer, Karam Khaddour, George Ansstas
Journal: Journal of the National Comprehensive Cancer Network (2023)

There is a lack of effective treatments for immunotherapy-refectory melanoma. Although PARP inhibitors (PARPi) are an effective treatment strategy in cancers with homologous recombination deficiency (HRD), determining HRD status is challenging in melanoma. Here, we chart the longitudinal relationship between PARPi response and HRD scores derived from genome-wide loss of heterozygosity (LOH) in 4 patients with metastatic melanoma. When next examining 933 melanoma cases, using an updated threshold, we observed HRD-related LOH (HRD-LOH) in nearly one-third of all cases compared with &lt;10% using traditional gene panels. Taken together, HRD-LOH in refractory melanoma is both a common occurrence and a potential biomarker for response to PARPi.
Counts, incidence rates, and trends of pediatric cancer in the United States, 2003-2019
Authors: David A Siegel, Jessica B King, Philip J Lupo, Eric B Durbin, Eric Tai, Kathi Mills, Elizabeth Van Dyne, Natasha Buchanan Lunsford, S Jane Henley, Reda J Wilson
Journal: JNCI Journal of the National Cancer Institute (2023)

Abstract Background Cancer is a leading cause of death by disease among children and adolescents in the United States. This study updates cancer incidence rates and trends using the most recent and comprehensive US cancer registry data available. Methods We used data from US Cancer Statistics to evaluate counts, age-adjusted incidence rates, and trends among children and adolescents younger than 20 years of age diagnosed with malignant tumors between 2003 and 2019. We calculated the average annual percent change (APC) and APC using joinpoint regression. Rates and trends were stratified by demographic and geographic characteristics and by cancer type. Results With 248 749 cases reported between 2003 and 2019, the overall cancer incidence rate was 178.3 per 1 million; incidence rates were highest for leukemia (46.6), central nervous system neoplasms (30.8), and lymphoma (27.3). Rates were highest for males, children 0 to 4 years of age, Non-Hispanic White children and adolescents, those in the Northeast census region, the top 25% of counties by economic status, and metropolitan counties with a population of 1 million people or more. Although the overall incidence rate of pediatric cancer increased 0.5% per year on average between 2003 and 2019, the rate increased between 2003 and 2016 (APC = 1.1%), and then decreased between 2016 and 2019 (APC = –2.1%). Between 2003 and 2019, rates of leukemia, lymphoma, hepatic tumors, bone tumors, and thyroid carcinomas increased, while melanoma rates decreased. Rates of central nervous system neoplasms increased until 2017, and then decreased. Rates of other cancer types remained stable. Conclusions Incidence of pediatric cancer increased overall, although increases were limited to certain cancer types. These findings may guide future public health and research priorities.
Inconsistent Data Between Distant Relapse Events and Breast Cancer–Specific Death Events in India Lidocaine Trial
Authors: Ke-Da Yu
Journal: Journal of Clinical Oncology (2023)

Badwe et al 1 conducted an open-label, multicenter randomized trial to test the impact of presurgical, peritumoral injection of 0.5% lidocaine on disease-free survival (DFS) and on overall survival (OS).At a median follow-up of 68 months, there were 255 DFS events and 189 deaths.In the local anesthetic (LA) and no-LA groups, 5-year DFS rates were 86.6% and 82.6% (hazard ratio [HR], 0.74; P 5 .017)and 5-year OS rates were 90.1% and 86.4% (HR, 0.71; P 5 .019),respectively.After reviewing the survival data, I am concerned about the inconsistency between recurrence and death events.
Caveolin Gene Expression Predicts Clinical Outcomes for Early-Stage HER2-Negative Breast Cancer Treated with Paclitaxel-Based Chemotherapy in the GeparSepto Trial
Authors: Terence M. Williams, Andreas Schneeweiss, Christian Jackisch, Changxian Shen, Karsten E. Weber, Peter A. Fasching, Carsten Denkert, Jenny Furlanetto, Ernst Heinmöller, Sabine Schmatloch, Thomas Karn, Christopher W. Szeto, Marion T. van Mackelenbergh, Valentina Nekljudova, Elmar Stickeler, Patrick Soon-Shiong, Christian Schem, Thomas Mairinger, Volkmar Müller, Frederik Marme, Michael Untch, Sibylle Loibl
Journal: Clinical Cancer Research (2023)

Caveolin-1 and -2 (CAV1/2) dysregulation are implicated in driving cancer progression and may predict response to nab-paclitaxel. We explored the prognostic and predictive potential of CAV1/2 expression for patients with early-stage HER2-negative breast cancer receiving neoadjuvant paclitaxel-based chemotherapy regimens, followed by epirubicin and cyclophosphamide.
Gastric antral defect closure after endoscopic submucosal dissection with the reopenable clip-over-the-line method using a multibending scope
Authors: Tatsuma Nomura, Shinya Sugimoto, Taishi Temma, Jun Oyamada, Keiichi Ito, Akira Kamei, Noriya Uedo
Journal: Endoscopy (2023)

Mucosal defect closure after gastric endoscopic submucosal dissection (ESD) is challenging because of the thick mucosal and muscle layers [1]; it is particularly difficult in the gastric antrum. When a conventional endoscope is pushed distally to access the antrum, the greater curvature is stretched. This widens the mucosal defect and stretches the muscle layer, making closure of the defect difficult ([Fig. 1]). Herein, we present a multibending scope technique that allows antral defect closure using the reopenable clip-over-the-line method (ROLM) to avoid stretching the muscle layer [2].
Use of mechanical lithotripter to assist in the endoscopic removal of an impacted long chicken bone in sigmoid diverticula
Authors: Eduardo Rodrigues-Pinto, Emanuel Dias, Renato Medas, Guilherme Macedo
Journal: Endoscopy (2023)

A 56-year-old woman without relevant medical history was admitted to the emergency room with persistent lower left abdominal pain for the previous 15 days. Abdominal computed tomography revealed diverticulosis of the left colon, with a 55-mm linear foreign body in the sigmoid colon, located transversely to the colon axis, with thickening of the bowel wall and adjacent fat, without perforation ([Fig. 1]). The patient was referred for endoscopic removal.
Ampullary Adenocarcinoma, Version 1.2023, NCCN Clinical Practice Guidelines in Oncology
Authors: E. Gabriela Chiorean, Marco Del Chiaro, Margaret A. Tempero, Mokenge P. Malafa, Al B. Benson, Dana B. Cardin, Jared A. Christensen, Vincent Chung, Brian Czito, Mary Dillhoff, Timothy R. Donahue, Efrat Dotan, Christos Fountzilas, Evan S. Glazer, Jeffrey Hardacre, William G. Hawkins, Kelsey Klute, Andrew H. Ko, John W. Kunstman, Noelle LoConte, Andrew M. Lowy, Ashiq Masood, Cassadie Moravek, Eric K. Nakakura, Amol K. Narang, Lorenzo Nardo, Jorge Obando, Patricio M. Polanco, Sushanth Reddy, Marsha Reyngold, Courtney Scaife, Jeanne Shen, Mark J. Truty, Charles Vollmer, Robert A. Wolff, Brian M. Wolpin, Beth McCullough RN, Senem Lubin, Susan D. Darlow
Journal: Journal of the National Comprehensive Cancer Network (2023)

Ampullary cancers refer to tumors originating from the ampulla of Vater (the ampulla, the intraduodenal portion of the bile duct, and the intraduodenal portion of the pancreatic duct), while periampullary cancers may arise from locations encompassing the head of the pancreas, distal bile duct, duodenum, or ampulla of Vater. Ampullary cancers are rare gastrointestinal malignancies, and prognosis varies greatly based on factors such as patient age, TNM classification, differentiation grade, and treatment modality received. Systemic therapy is used in all stages of ampullary cancer, including neoadjuvant therapy, adjuvant therapy, and first-line or subsequent-line therapy for locally advanced, metastatic, and recurrent disease. Radiation therapy may be used in localized ampullary cancer, sometimes in combination with chemotherapy, but there is no high-level evidence to support its utility. Select tumors may be treated surgically. This article describes NCCN recommendations regarding management of ampullary adenocarcinoma.
Fibrotic Marker Galectin-3 Identifies Males at Risk of Developing Cancer and Heart Failure
Authors: Pieter F. van den Berg, Joseph Pierre Aboumsallem, Elles M. Screever, Canxia Shi, Sanne de Wit, Valentina Bracun, Laura I. Yousif, Lotte Geerlings, Dongyu Wang, Jennifer E. Ho, Stephan J.L. Bakker, Bert van der Vegt, Herman H.W. Silljé, Rudolf A. de Boer, Wouter C. Meijers
Journal: JACC CardioOncology (2023)

Cancer and heart failure (HF) are the leading causes of death in the Western world. Shared mechanisms such as fibrosis may underlie either disease entity, furthermore it is unknown whether this relationship is sex-specific.We sought to investigate how fibrosis-related biomarker galectin-3 (gal-3) aids in identifying individuals at risk for new-onset cancer and HF, and how this differs between sexes.Gal-3 was measured at baseline and at 4-year follow-up in 5,786 patients of the PREVEND (Prevention of Renal and Vascular Endstage Disease) study. The total follow-up period was 11.5 years. An increase of ≥50% in gal-3 levels between measurements was considered relevant. We performed sex-stratified log-rank tests and Cox regression analyses overall and by sex to evaluate the association of gal-3 over time with both new-onset cancer and new-onset HF.Of the 5,786 healthy participants (50% males), 399 (59% males) developed new-onset cancer, and 192 (65% males) developed new-onset HF. In males, an increase in gal-3 was significantly associated with new-onset cancer (both combined and certain cancer-specific subtypes), after adjusting for age, body mass index, hypertension, smoking status, estimated glomerular filtration rate, diabetes mellitus, triglycerides, coronary artery disease, and C-reactive protein (HR: 1.89; 95% CI: 1.32-2.71; P < 0.001). Similar analyses demonstrated an association with new-onset HF in males (HR: 1.77; 95% CI: 1.07-2.95; P = 0.028). In females, changes in gal-3 over time were neither associated with new-onset cancer nor new-onset HF.Gal-3, a marker of fibrosis, is associated with new-onset cancer and new-onset HF in males, but not in females.
Impact of immune checkpoint inhibitors on atherosclerosis progression in patients with lung cancer
Authors: Zsofia Dora Drobni, Carlos Gongora, Jana Taron, Giselle A Suero-Abreu, Julia Karady, Hannah K Gilman, Sama Supraja, Sofia Nikolaidou, Nicolas Leeper, Béla Merkely, Pal Maurovich-Horvat, Borek Foldyna, Tomas G Neilan
Journal: Journal for ImmunoTherapy of Cancer (2023)

Patients with lung cancer face a heightened risk of atherosclerosis-related cardiovascular events. Despite the strong scientific rationale, there is currently a lack of clinical evidence examining the impact of immune checkpoint inhibitors (ICIs) on the advancement of atherosclerosis in patients with lung cancer. The objective of our study was to investigate whether there is a correlation between ICIs and the accelerated progression of atherosclerosis among individuals with lung cancer.
Inferior Outcomes of EU Versus US Patients Treated With CD19 CAR-T for Relapsed/Refractory Large B-cell Lymphoma: Association With Differences in Tumor Burden, Systemic Inflammation, Bridging Therapy Utilization, and CAR-T Product Use
Authors: Veit Bücklein, Ariel Perez, Kai Rejeski, Gloria Iacoboni, Vindi Jurinovic, Udo Holtick, Olaf Penack, Soraya Kharboutli, Viktoria Blumenberg, Josephine Ackermann, Lisa Frölich, Grace Johnson, Kedar Patel, Brian Arciola, Rahul Mhaskar, Anthony Wood, Christian Schmidt, Omar Albanyan, Philipp Gödel, Eva Hoster, Lars Bullinger, Andreas Mackensen, Frederick Locke, Michael von Bergwelt, Pere Barba, Marion Subklewe, Michael D. Jain
Journal: HemaSphere (2023)

Real-world evidence suggests a trend toward inferior survival of patients receiving CD19 chimeric antigen receptor (CAR) T-cell therapy in Europe (EU) and with tisagenlecleucel. The underlying logistic, patient- and disease-related reasons for these discrepancies remain poorly understood. In this multicenter retrospective observational study, we studied the patient-individual journey from CAR-T indication to infusion, baseline features, and survival outcomes in 374 patients treated with tisagenlecleucel (tisa-cel) or axicabtagene-ciloleucel (axi-cel) in EU and the United States (US). Compared with US patients, EU patients had prolonged indication-to-infusion intervals (66 versus 50 d; P &lt; 0.001) and more commonly received intermediary therapies (holding and/or bridging therapy, 94% in EU versus 74% in US; P &lt; 0.001). Baseline lactate dehydrogenase (LDH) (median 321 versus 271 U/L; P = 0.02) and ferritin levels (675 versus 425 ng/mL; P = 0.004) were significantly elevated in the EU cohort. Overall, we observed inferior survival in EU patients (median progression-free survival [PFS] 3.1 versus 9.2 months in US; P &lt; 0.001) and with tisa-cel (3.2 versus 9.2 months with axi-cel; P &lt; 0.001). On multivariate Lasso modeling, nonresponse to bridging, elevated ferritin, and increased C-reactive protein represented independent risks for treatment failure. Weighing these variables into a patient-individual risk balancer (high risk [HR] balancer), we found higher levels in EU versus US and tisa-cel versus axi-cel cohorts. Notably, superior PFS with axi-cel was exclusively evident in patients at low risk for progression (according to the HR balancer), but not in high-risk patients. These data demonstrate that inferior survival outcomes in EU patients are associated with longer time-to-infusion intervals, higher tumor burden/LDH levels, increased systemic inflammatory markers, and CAR-T product use.